The reasons for the widely different sensitivity of different cell lines to the antiproliferative effects of interferon is not understood. Our working hypothesis is that some cell lines may have a vastly different number of receptors for interferon. Cells with the greatest number of receptors may be the most sensitive to the antiproliferative effects. We will measure the number of receptors in different cell lines and correlate this number with the other activities induced by interferon. We do not know, for example, which receptor occupancy is required to obtain a biological response. To standardize a biological response test, we will measure the activity of the enzyme 2-5A synthetase, the synthesis of which is induced by interferon. Parallel studies will investigate the fate of interferon bound to cellular receptors and the mechanism of action of the interferon/receptor complex. Questions related to the internalization of the cell-bound interferon and the regulation of the receptor number will be addressed in these studies. These investigations may provide relevant information for treating different cells with interferon as an antiproliferative agent.